共查询到20条相似文献,搜索用时 15 毫秒
1.
Moni Sharma Kuldeep Chauhan Rajeev K. Srivastava Shiv V. Singh Kumkum Srivastava Jitendra K. Saxena Sunil K. Puri Prem M. S. Chauhan 《Chemical biology & drug design》2014,84(2):175-181
A series of novel 4‐aminoquinolinyl and 9‐anilinoacridinyl Schiff base hydrazones have been synthesized and evaluated for their antimalarial activity. All compounds were evaluated in vitro for their antimalarial activity against chloroquine‐sensitive strain 3D7 and the chloroquine‐resistant K1 strain of Plasmodium falciparum and for cytotoxicity toward Vero cells. Compounds 17 , 20 , and 21 displayed good activity against the 3D7 strain with IC50 values ranging from 19.69 to 25.38 nm . Moreover, compounds 16 , 17 , 21 , 24 , 32, and 33 exhibited excellent activities (21.64–54.26 nm ) against K1 strain and several compounds displayed β‐hematin inhibitory activity, suggesting that they act on the heme crystallization process such as CQ. Compounds were also found to be non‐toxic with good selectivity index. 相似文献
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Yong Yin Shao Sha Yan‐Ting Wang Xun Wu She‐Feng Wang Fang Qiao Peng‐Cheng Lv Hai‐Liang Zhu 《Chemical biology & drug design》2015,86(5):1323-1329
VEGFR2 has been proved to play a major role in the regulation of tumor angiogenesis. Twenty‐one 4‐alkoxyquinazoline‐based derivatives have been designed and synthesized as vascular endothelial growth factor receptor 2 (VEGFR2) inhibitors, and their biological activities were evaluated. Among these compounds, compound 3h exhibited the most potent inhibitory activities against VEGFR2 tyrosine kinase and cell proliferation, with the IC50 values of 2.89 nm (for VEGFR2) and 0.25 μ m (for MCF‐7), which were comparable with the control compound. Docking simulation was performed to position compound 3h into the 4ASE active site, and the result showed that compound 3h could bind well at the 4ASE active site. 相似文献
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《Journal of labelled compounds & radiopharmaceuticals》2004,47(1):31-36
Two 1,2,3‐triazoline anticonvulsants, 1‐(4‐methylsulphone‐phenyl)‐5‐(4‐methoxy‐phenyl)‐1,2,3‐triazoline and l‐(4‐methylsulphone‐phenyl)‐5‐phenyl‐1,2,3‐triazoline, both labelled with carbon‐14 in the 5‐position, have been synthesized as part of a 5‐step sequence. Copyright © 2003 John Wiley & Sons, Ltd. 相似文献
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Grazyna Weltrowska Thi M.‐D. Nguyen Carole Lemieux Nga N. Chung Peter W. Schiller 《Chemical biology & drug design》2008,72(5):337-340
Analogues of the opioid peptides H‐Tyr‐c[d ‐Cys‐Gly‐Phe(pNO2)‐d ‐Cys]NH2 (non‐selective), H‐Tyr‐d ‐Arg‐Phe‐Lys‐NH2 (μ‐selective) and dynorphin A(1‐11)‐NH2 (κ‐selective) containing 4′‐[N‐((4′‐phenyl)‐phenethyl)carboxamido]phenylanine (Bcp) in place of Tyr1 were synthesized. All three Bcp1‐opioid peptides retained high μ opioid receptor binding affinity, but showed very significant differences in the opioid receptor selectivity profiles as compared with the corresponding Tyr1‐containing parent peptides. The cyclic peptide H‐Bcp‐c[d ‐Cys‐Gly‐Phe(pNO2)‐d ‐Cys]NH2 turned out to be an extraordinarily potent, μ‐selective opioid agonist, whereas the Bcp1‐analogue of dynorphin A(1‐11)‐NH2 displayed partial agonism at the μ receptor. The obtained results suggest that the large biphenylethyl substituent contained in these compounds may engage in a hydrophobic interaction with a receptor subsite and thereby may play a role in the ligand’s ability to induce a specific receptor conformation or to bind to a distinct receptor conformation in a situation of conformational receptor heterogeneity. 相似文献
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V. Alagarsamy S. Meena K.V. Ramseshu V. Raja Solomon K. Thirumurugan 《Drug development research》2008,69(4):226-233
A new series of 3‐(4‐chloro phenyl)‐2‐substituted‐3H‐quinazolin‐4‐ones were synthesized by reacting the amino group of 2‐hydrazino‐3‐(4‐chloro phenyl)‐3H‐quinazolin‐4‐one with different aldehydes and ketones. The compounds were investigated for their analgesic activity in albino mice, and for their anti‐inflammatory and ulcerogenic activities in Wistar rats. All test compounds exhibited analgesic and anti‐inflammatory activities. Compound VA2 (2‐(1‐ethylpropylidene‐hydrazino)‐3‐(4‐chloro phenyl)‐3H‐quinazolin‐4‐one) showed moderately more potent analgesic activity and compound VA3 (2‐(1‐methylbutylidene‐hydrazino)‐3‐(4‐chlorophenyl)‐3H‐quinazolin‐4‐one) showed moderately more potent anti‐inflammatory activity when compared with the reference standard, diclofenac sodium. The test compounds showed only mild ulcerogenic side effects when compared with aspirin. Drug Dev Res 69: 226–233, 2008 ©2008 Wiley‐Liss, Inc. 相似文献
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Majid Mahmoodi Alireza Aliabadi Saeed Emami Maliheh Safavi Saeed Rajabalian Mohammad‐Ali Mohagheghi Ahad Khoshzaban Alireza Samzadeh‐Kermani Navid Lamei Abbas Shafiee Alireza Foroumadi 《Archiv der Pharmazie》2010,343(7):411-416
A new series of 4‐aryl‐4H‐chromenes bearing a 2‐arylthiazol‐4‐yl moiety at the 4‐position were prepared as potential cytotoxic agents. The in‐vitro cytotoxic activity of the synthesized 4‐aryl‐4H‐chromenes was investigated in comparison with etoposide, a well‐known anticancer drug, using MTT colorimetric assay. Among them, the 2‐(2‐chlorophenyl)thiazol‐4‐yl analog 4b showed the most potent activity against nasopharyngeal epidermoid carcinoma KB, medulloblastoma DAOY, and astrocytoma 1321N1, and compound 4d bearing a 2‐(4‐chlorophenyl)thiazol‐4‐yl moiety at the 4‐position of the chromene ring exhibited the best inhibitory activity against breast cancer cells MCF‐7, lung cancer cells A549, and colon adenocarcinoma cells SW480 with IC50 values less than 5 μM. The ability of compound 4b to induce apoptosis was confirmed in a nuclear morphological assay by DAPI staining in the KB and MCF‐7 cells. 相似文献
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Design,synthesis, and negative inotropic evaluation of 4‐phenyl‐1H‐1,2,4‐triazol‐5(4H)‐one derivatives containing triazole or piperazine moieties 下载免费PDF全文
Zhi‐Yu Wei Bai‐Ri Cui Xun Cui Yan‐Ling Wu Yang Fu Li‐Ping Liu Hu‐Ri Piao 《Chemical biology & drug design》2017,89(1):47-60
In this study, four novel series of 4‐phenyl‐1H ‐1,2,4‐triazol‐5(4H )‐one derivatives containing triazole or piperazine moieties were designed, synthesized, and evaluated for negative inotropic activity by measuring the left atrium stroke volume in isolated rabbit heart preparations. Almost all of the compounds showed an ability to moderate the cardiac workload by decreasing the heart rate and contractility. Among them, 7h was found to be the most potent with a change in stroke volume of ?48.22 ± 0.36% at a concentration of 3 × 10?5 mol/L (metoprolol: ?9.74 ± 0.14%). The cytotoxicity of these compounds was evaluated using the human cervical cancer cell line HeLa, the liver cancer cell line Hep3B, and the human normal hepatic cell line LO 2. A preliminary study of the mechanism of action for the compound 7h on the regulation of atrial dynamics with ATP ‐sensitive K+ channel and L‐type Ca2+ channel blockers glibenclamide and nifedipine was performed in the isolated perfused beating rabbit atria. 相似文献
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Synthesis of Novel Pyrimidin‐4‐One Bearing Piperazine Ring‐Based Amides as Glycogen Synthase Kinase‐3β Inhibitors with Antidepressant Activity 下载免费PDF全文
Imran Khan Mushtaq A. Tantray Hinna Hamid Mohammad Sarwar Alam Abul Kalam Faraz Shaikh Anamik Shah Firasat Hussain 《Chemical biology & drug design》2016,87(5):764-772
Novel pyrimidin‐4‐one derivatives have been synthesized using EDC coupling and evaluated as glycogen synthase kinase‐3β (GSK‐3β) inhibitors. Among all the synthesized compounds, compound 5 (3‐methyl‐6‐phenyl‐2‐(piperazin‐1‐yl)‐3,4‐dihydropyrimidin‐4‐one) exhibited the most potent inhibitory activity against GSK‐3β with IC50 value of 74 nm . The molecular docking studies were performed to elucidate the binding modes of the compounds with the target, and a crucial interaction involving hydrogen bond formation with Val‐135 to the active site of GSK‐3β was observed. Furthermore, the synthesized compounds were subjected to in vivo evaluation of their antidepressant activity, and compound 5 showing highest inhibition of GSK‐3β was also found to significantly reduce the duration of immobility at 50 mg/kg, when compared with fluoxetine, a known antidepressant drug. The results of our study suggest that compound 5 may serve as a valuable template for the design and development of inhibitors of GSK‐3β with antidepressant activity. 相似文献
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Organocatalyzed Novel Synthetic Methodology for Highly Functionalized Piperidines as Potent α‐Glucosidase Inhibitors 下载免费PDF全文
Ariba Farooq Lubna Shahazadi Marek Bajda Nisar Ullah Abdul Rauf Sohail Anjum Shahzad Ather Farooq Khan Muhammad Ashraf Muhammad Yar 《Archiv der Pharmazie》2016,349(9):724-732
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Discovery of Novel 2‐(piperidin‐4‐yl)‐1H‐benzo[d]imidazole Derivatives as Potential Anti‐Inflammatory Agents 下载免费PDF全文
Xinning Wang Yang Zong Leilei Zhao Junhao Xing Jinpei Zhou Huibin Zhang 《Chemical biology & drug design》2015,86(4):509-516
A novel 2‐(piperidin‐4‐yl)‐1H‐benzo[d]imidazole derivative 5 with good anti‐inflammatory activity was identified from our in‐house library. Based on hit compound 5 , two series of 2‐(piperidin‐4‐yl)‐1H‐benzo[d]imidazole derivative 6a – g and 7a – h were designed and synthesized as novel anti‐inflammatory agents. Most of synthesized compounds exhibited good inhibitory activity on NO and TNF‐α production in LPS‐stimulated RAW 264.7 macrophages, in which the compound 6e showed most potent inhibitory activity on NO (IC50 = 0.86 μm ) and TNF‐α (IC50 = 1.87 μm ) production. Further evaluation revealed that compound 6e displayed more potent in vivo anti‐inflammatory activity than ibuprofen did on xylene‐induced ear oedema in mice. Additionally, Western blot analysis revealed that compound 6e could restore phosphorylation level of IκBα and protein expression of p65 NF‐κB in LPS‐stimulated RAW 264.7 macrophages. 相似文献
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Anxiolytic‐like effect of 2‐(4‐((1‐phenyl‐1H‐pyrazol‐4‐yl)methyl)piperazin‐1‐yl)ethan‐1‐ol is mediated through the benzodiazepine and nicotinic pathways 下载免费PDF全文
Adriane F. Brito James O. Fajemiroye Hiasmin F. S. Neri Dayane M. Silva Daiany P. B. Silva Germán Sanz Boniek G. Vaz Flávio S. de Carvalho Paulo C. Ghedini Luciano M. Lião Ricardo Menegatti Elson A. Costa 《Chemical biology & drug design》2017,90(3):432-442
In this study, we proposed the design, synthesis of a new compound 2‐(4‐((1‐phenyl‐1H‐pyrazol‐4‐yl)methyl)piperazin‐1‐yl)ethan‐1‐ol (LQFM032), and pharmacological evaluation of its anxiolytic‐like effect. This new compound was subjected to pharmacological screening referred to as Irwin test, prior to sodium pentobarbital‐induced sleep, open‐field and wire tests. The anxiolytic‐like effect of this compound was evaluated using elevated plus maze and light–dark box tests. In addition, the mnemonic activity was evaluated through step‐down test. In sodium pentobarbital‐induced sleep test, LQFM032 decreased latency and increased duration of sleep. In the open‐field test, LQFM032 altered behavioral parameter, that suggested anxiolytic‐like activity, as increased in crossings and time spent at the center of open field. In the plus maze test and light–dark box test, the LQFM032 showed anxiolytic‐like activity, increased entries and time spent on open arms, and increased in number of transitions and time spent on light area, respectively. Those effects was antagonized by flumazenil but not with 1‐(2‐Methoxyphenyl)‐4‐(4‐phthalimidobutyl)piperazine (NAN‐190). The LQFM032 did not alter mnemonic activity. Moreover, the anxiolytic‐like activity of LQFM032 was antagonized by mecamylamine. In summary, LQFM032 showed benzodiazepine and nicotinic pathways mediated anxiolytic‐like activity without altering the mnemonic activity. 相似文献
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Elaine S. Coimbra Luciana M. R. Antinarelli Adilson D. da Silva Marcelle L. F. Bispo Carlos R. Kaiser Marcus V. N. de Souza 《Chemical biology & drug design》2013,81(5):658-665
In this work, we report the antileishmanial evaluation of twenty 7‐chloro‐4‐quinolinyl hydrazone derivatives ( 1 – 20 ). Firstly, the compounds were tested against promastigotes of four different Leishmania species. After that, all derivatives were assayed against L. braziliensis amastigotes and murine macrophages. Furthermore, it was investigated whether the antiamastigote L. braziliensis effect of the compounds could be associated with nitric oxide production. Compounds 6 and 7 showed a strong leishmanicidal activity against intracellular parasite with IC50 in nanogram levels (30 and 20 ng/mL, respectively). Appreciable activity of three compounds tested can be considered an important finding for the rational design of new leads for antileishmanial compounds. 相似文献
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Imen Boualia Chamseddine Derabli Raouf Boulcina Chawki Bensouici Muhammet Yildirim Arzu Birinci Yildirim El Hassen Mokrani Abdelmadjid Debache 《Archiv der Pharmazie》2019,352(11)
A series of bis(4‐amino‐5‐cyano‐pyrimidines) was synthesized and evaluated as dual inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). To further explore the multifunctional properties of the new derivatives, their antioxidant and antibacterial activities were also tested. The results showed that most of these compounds could effectively inhibit AChE and BChE. Particularly, compound 7c exhibited the best AChE inhibitory activity (IC50 = 5.72 ± 1.53 μM), whereas compound 7h was identified as the most potent BChE inhibitor (IC50 = 12.19 ± 0.57 μM). Molecular modeling study revealed that compounds 7c, 7f , and 7b showed a higher inhibitory activity than that of galantamine against both AChE and BChE. Anticholinesterase activity of compounds 7h, 7b , and 7c was significant in vitro and in silico for both enzymes, since these compounds have hydrophobic rings (Br‐phenyl, dimethyl, and methoxyphenyl), which bind very well in both sites. In addition to cholinesterase inhibitory activities, these compounds showed different levels of antioxidant activities. Indeed, in the superoxide–dimethyl sulfoxide alkaline assay, compound 7j showed very high inhibition (IC50 = 0.37 ± 0.28 μM). Also, compound 7l exhibited strong and good antibacterial activity against Staphylococcus epidermidis and Staphylococcus aureus, respectively. Taking into account the results of biological evaluation, further modifications will be designed to increase potency on different targets. In this study, the obtained results can be a new starting point for further development of multifunctional agents for the treatment of Alzheimer's disease. 相似文献
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Synthesis and Biological Evaluation of Novel FtsZ‐targeted 3‐arylalkoxy‐2,6‐difluorobenzamides as Potential Antimicrobial Agents 下载免费PDF全文
Shengsheng Qiang Changde Wang Henrietta Venter Xin Li Yi Wang Liwei Guo Ruixin Ma Shutao Ma 《Chemical biology & drug design》2016,87(2):257-264
Novel series of 3‐O‐arylalkylbenzamide and 3‐O‐arylalkyl‐2,6‐difluorobenzamide derivatives were synthesized and evaluated for their on‐target activity and antibacterial activity. The results indicated that the 3‐O‐arylalkyl‐2,6‐difluorobenzamide derivatives possessed much better on‐target activity and antibacterial activity than the 3‐O‐arylalkylbenzamide derivatives. Among them, 3‐O‐chlorobenzyl derivative 36 was the most effective in antibacterial activity (0.5, 4, and 8 μg/mL) against Bacillus subtilis ATCC9372, methicillin‐resistant Staphylococcus aureus ATCC29213, and penicillin‐resistant Staphylococcus aureus PR, while 3‐O‐methylbenzyl derivative 41 only exhibited the most potent activity (2 μg/mL) against Staphylococcus aureus ATCC25923. 相似文献
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Peter L. Johnson Norman R. Pearson Bert Schuster Jeremy Cobb 《Journal of labelled compounds & radiopharmaceuticals》2009,52(9):382-386
Pentachloropyridine serves as a key intermediate in the synthesis of 4‐amino‐3,5,6‐trichloropicolinic acid (picloram) and 4‐amino‐3,6‐dichloropicolinic acid (aminopyralid). An M+3 stable isotope of pentachloropyridine (1, pentachloropyridine‐1‐15N‐2,6‐13C2) was prepared from K13C15N. Isotopically labeled pentachloropyridine was then carried through a seven‐step synthesis to give an M+3 stable isotope of 4‐amino‐3,5,6‐trichloropicolinic acid (2, picloram‐1‐15N‐2,6‐13C2) in an overall yield of 42%. The chlorine atom in the 5‐position of 2 was selectively removed via electrochemical reduction. Carrying out the electrochemical reduction in water provided an M+3 stable isotope of 4‐amino‐3,6‐dichloropicolinic acid (3, aminopyralid‐1‐15N‐2,6‐13C2), whereas conducting the reduction in deuterium oxide produced an M+4 stable isotope (4, aminopyralid‐1‐15N‐2,6‐13C2‐5‐2H). Copyright © 2009 John Wiley & Sons, Ltd. 相似文献